Prior epidemiological and experimental data suggests a J-shaped relationship between number of pregnancies (parity) and later-life maternal cardiovascular disease (CVD) and congestive heart failure. Thus excess CVD risk is present for nulliparous women as well as those with increasing number of pregnancies beyond two term deliveries. Nulliparity is associated with conditions that lead to infertility such as polycystic ovarian disease, which in turn is very closely linked with CVD risk factors. However, it is unknown whether a general history of involuntary childlessness among women who eventually conceive also confers an increased risk of later life CVD. Pregnancy and the peripartum period are associated with marked maternal cardiovascular/ hemodynamic adaptations. However, it is uncertain whether these changes result in long term alterations in left ventricular (LV) structure and function. We propose a prospective study of reproductive factors and maternal cardiovascular disease which aims to fill in these knowledge gaps. This will be accomplished in the context of two well-characterized populations: 1. The Swedish National Population Registries and 2. The Multiethnic Study of Atherosclerosis (MESA). Thus, the three main aims of this study are to: 1) To prospectively evaluate whether a history of involuntary childlessness is a risk factor for incident CVD among women later having term pregnancies 2) To prospectively examine the association between parity and LV structure and function and 3) To prospectively examine the association between parity and coronary artery calcification. Specifically, we hope to determine whether the association between parity and maternal CVD is mediated by coronary atherosclerosis (as measured by coronary artery calcification). PUBLIC HEALTH RELEVANCE: Cardiovascular disease is considered a life course disease, beginning in the prenatal period and progressing until senescence, with a pathophysiologic continuum ranging from cardiovascular risk factors, through subclinical disease, to overt disease and death. Whereas postmenopausal risk factors have been fairly well-studied in women, reproductive factors in relation to CVD in women have not been equally well-examined. Our hope is that by better characterizing reproductive cardiovascular risk factors we will make significant contributions to CVD risk stratification among younger women that will hopefully lead to upstream CVD prevention.